Citalopram and escitalopram

Citalopram (Ceiexa), Esdtalopram (Lexapro). Escitalopram is the enantiomer S-citalopram. Citalopram is a 50 50 mixtnre of s- and r-citalopram of which the former is the active component. Both are very selective SSRIs. The side effects of citalopram and escitalopram appear to be comparable to other SSRIs. 

Hepatic metabolism of citalopram and escitalopram occurs primarily through cytochrome P450 3A4 and 2C19 isoenzymes. Inhibitors of 3A4 (eg, azole antifungals, macrolide antibiotics) and 2C19 (eg, omeprazole) would be expected to increase plasma citalopram levels. Inducters of 3A4 (eg, carbamazepine) would be expected to decrease citalopram and escitalopram levels. 

The most common interactions with SSRIs are pharmacokinetic interactions. For example, paroxetine and fluoxetine are potent CYP2D6 inhibitors (Table 30-4). Thus, administration with 2D6 substrates such as TCAs can lead to dramatic and sometimes unpredictable elevations in the tricyclic drug concentration. The result may be toxicity from the TCA. Similarly, fluvoxamine, a CYP3A4 inhibitor, may elevate the levels of concurrently administered substrates for this enzyme such as diltiazem and induce bradycardia or hypotension. Other SSRIs, such as citalopram and escitalopram, are relatively free of pharmacokinetic interactions. The most serious interaction with the SSRIs are pharmacodynamic interactions with MAOIs that produce a serotonin syndrome (see below). 

The selective serotonin re-uptake inhibitors (SSRIs) that are currently available are fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, and escitalopram. They are widely marketed and are in many countries a major alternative to tricyclic antidepressants in the treatment of depression. The SSRIs are structurally diverse, but they are all inhibitors of serotonin uptake, with much less effect on noradrenaline. They have slight or no inhibitory effect on histaminergic, adrenergic, serotonergic, dopaminergic, and cholinergic receptors (1). 

Citalopram and escitalopram are major substrates of CYP2C19 and CYP3A4, and weakly inhibit CYP2D6. 

Escitalopram oxalate is the 5-enantiomer of citalopram (5). The therapeutic activity of citalopram resides in the 5-isomer and escitalopram binds with high affinity to the human serotonin transporter R-citalopram is about 30-fold less potent. The half-life of escitalopram is 27-32 hours. Citalopram and escitalopram have negligible effects on CYP isozymes. 

Citalopram and escitalopram CYP2C19 PMs may respond better to average doses [47]. CYP2C19 UMs may need higher doses [47,64]. 

Paroxetine, sertraline, citalopram and escitalopram, fluvoxamine and venlafaxine are... 

Fluoxetine can increase serum pindolol and carvedilol levels, but the clinical effects of this are minimal. Isolated reports describe lethargy and bradycardia in patients taking metoprolol with fluoxetine and propranolol with fluoxetine or fluvoxamine. Flu-voxamine may increase the levels of propranolol, but not atenolol. Paroxetine may increase levels of metoprolol resulting in increased beta-blocking effects. Citalopram and escitalopram may interact similarly. Sertraline does not interact with atenolol. 

Fluoxetine and paroxetine inhibit the cytochrome P450 isoenzyme CYP2D6 thus inhibiting the metabolism of some beta blockers (e.g. propranolol, metoprolol, carvedilol) so that they accumulate, the result being that their effects, such as bradycardia, may be increased. Citalopram and escitalopram may also inhibit CYP2D6. In vitro studies with human liver microsomes found that fluoxetine and paroxetine are potent inhibitors of metoprolol metabolism and fluvoxamine, sertraline and citalopram less potent. However, fluvoxamine also potently inhibits the metabolism of propranolol by CYP1A2. Beta blockers that are not extensively me-... 

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